The long term objectives of this proposal are to determine the ability of human antibody responses to abrogate the pathogenic potential of the periodontopathogen, A. actinomycetemcomitans. To progress towards this goal, the function and specificity of the complex humoral response to the microorganisms must be disected. The specific aims of the project are: 1) to isolate immunodominant surface antigens from A. actinomycetemcomitans and 2) to develop human hybridomas producing monoclonal antibodies to these antigens. It is well established that in the course of natural bacterial infections, the host responds with the formation of antibodies to a wide range of different antigens, including extracellular products, cell wall constituents, and cytoplasmic components that are expressed by the infecting organism. This extensive response is not entirely necessary for control of the infection, but there is a degree of selectivity in the response that appears to focus on the extracellular products and the surface antigenic constituents. This proposal will therefore concentrate on the surface antigens of A. actinomycetemcomitans. Somatic cell hybridization procedures have dramatically altered and broadened the scope of immunologic research. While this technology in the murine system and the procedures employed have rapidly increased our knowledge in many areas, the ability to elucidate the detailed interactions between the human antibody response and bacterial infectious agents can not progress utilizing murine hybridoma products. A strategic benefit would be gained in clinical immunology research if methods were available for the reproducible generation of human monoclonal antibodies. The possible applications could have a major impact on monitoring and maintaining human homeostasis with the environment. The development of human hybridomas producing monoclonal antibodies to environment. The development of human hybridomas producing monoclonal antibodies to the A. actinomycetemcomitans antigens should be valuable in the progress of periodontal research by defining significant surface antigens from A. actinomycetemcomitans and it may be anticipated that the acquisition of human monoclonals can then be used to analyze immunologic interference with A. actinomycetemcomitans virulence. These antibodies will provide new directions for addressing the importance of the humoral immune response in protection from disease caused by the microorgansim.